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A randomized, double-blind placebo-controlled phase I clinical study on safety and efficacy of the G-Rup® syrup (a mixture of ginger extract and honey) in symptomatic treatment of knee osteoarthritis
No full textWhat is known and Objectives: Present study evaluated the safety profile and efficacy of G-Rup® syrup (100 mg/ml ginger extract plus 150 mg/ml honey) in symptomatic treatment of knee osteoarthritis (OA). Methods: Patients diagnosed with knee OA were randomly assigned (1:1) to receive either of a 30 ml twice daily regimen of G-Rup® syrup or placebo over a 12-week period. Primary endpoints of the study comprised of an improvement in the joint's stiffness, physical functioning and pain score, assessed by WOMAC questionnaire and the visual analog scale (VAS). Secondary objectives comprised of safety and tolerability of the syrup by patients. Results and discussion: The 30 ml twice-daily regimen of G-Rup® syrup was safe and well tolerated by patients. Moreover, in whole studied time points, treatment with G-Rup® syrup could significantly Power the VAS score (p < 0.001) whereas improving WOMAC total score (p < 0.001) and pain (p < 0.001), physical functioning (p < 0.001), and stiffness sub-scores (p = 0.006) compared to the placebo receiving group. What is new and Conclusion: Based on obtained results, the G-Rup® syrup, composed of a combination of honey and ginger, may be a proper supplementary choice, along with routine therapeutic regimens, for improvement of symptomatic treatment of OA. © 2022 John Wiley & Sons Ltd
Targeted regulation of autophagy using nanoparticles: New insight into cancer therapy
No full textNormal cells depend on autophagy to maintain cellular homeostasis by recycling damaged organelles and misfolded proteins and degrading toxic agents. Similar to apoptosis, targeting autophagy has been under attention in cancer therapy. However, autophagy has both pro-survival and pro-death functions in tumors, and its targeting requires further elucidation. The current review focuses on using nanoparticles for targeting autophagy in cancer treatment. Nanocarriers can deliver autophagy regulators along with chemotherapeutic agents leading to intracellular accumulation in cancer cells and synergistic cancer therapy. Furthermore, genetic tools such as siRNA and shRNA can be used for targeting molecular components that regulate autophagy, such as the ATG12-ATG5-ATG16L1 complex. A number of nanostructures, such as gold and zinc oxide nanoparticles, can be used to enhance oxidative stress-mediated apoptosis and autophagy, reducing cancer progression. Further, using nanoparticles to modulate autophagy potentiates the anti-tumor effects of cisplatin and gefitinib during chemotherapy. Polymeric nanoparticles, lipid-based nanostructures and carbon-based nanomaterials are among other nanoparticles capable of regulating autophagy in cancer cells. Of note, various regulatory components of autophagy such as ATGs, Beclin-1 and LC3-II can be affected by nanomaterials. Based on the role of nanomaterial-induced autophagy as pro-survival or pro-death, further targeting can potentiate the fight against cancer cells. © 2021 Elsevier B.V
In vitro release and cytotoxicity study of encapsulated sulfasalazine within LTSP micellar/liposomal and TSP micellar/niosomal nano-formulations
No full textThe micelles/liposome formulation for the first time has been constructed via thin-film hydration method containing soy lecithin (L), tween 80 (T), squalene (S), and polyvinyl alcohol (P) (LTSP nanoparticles). Similar ingredients except for lecithin were used for preparing micellar/niosomal vesicular SSZ nanoformulation (TSP nanoparticles). The percent drug loading and encapsulation efficiency of SSZ was 7.39 and 98.5 ± 0.3 for the 7.5:100 (w/w) ratio of SSZ: total weight of LTSP, while the percent drug loading and encapsulation efficiency of SSZ was 4.7 and 62.85 ± 0.3 in the TSP nanoformulation. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that both formulations formed spherical micelles and vesicles with globule sizes of 25 ± 1.2 nm and 100 ± 20.5 nm respectively. The cell toxicity evaluations showed that both LTSP and TSP nanoformulations without drug were nontoxic (at the range of this experiment) for Human Dermal Fibroblasts (HDF) as a normal cell line but SSZ loaded nanoformulation exhibited increased cell toxicity with half-maximal inhibitory concentration (IC50) of 940 µM for SSZ alone to near 240 µM for SSZ loaded nanoformulation (approximately four times). In vitro release experiments exhibited sustained release of SSZ from both nanoformulations. The LTSP micellar/liposomal and TSP micellar/niosomal nanoformulation for SSZ delivery can be considered as appropriate approaches for improving its bioavailability and probably they are good candidates for future clinical investigations. © 2022 Faculty of Engineering, Alexandria Universit
Randomized controlled trial of astaxanthin impacts on antioxidant status and assisted reproductive technology outcomes in women with polycystic ovarian syndrome
No full textPurpose: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is typically accompanied by a defective oxidative defense system. Here, we investigated the effect of astaxanthin (AST) as a powerful antioxidant on the oxidative stress (OS) response and assisted reproductive technology (ART) outcomes in PCOS patients. Methods: In this double-blind, randomized, placebo-controlled trial, PCOS patients were randomly assigned into two groups. The intervention group received 8 mg AST, and the control group received the placebo daily for 40 days. The primary outcomes were the serum and follicular fluid (FF) levels of the OS biomarkers and the expression levels of the specific genes and proteins in the oxidative stress response pathway. The secondary outcomes were considered ART outcomes. Results: According to our findings, a 40-day course of AST supplementation led to significantly higher levels of serum CAT and TAC in the AST group compared to the placebo group. However, there were no significant intergroup differences in the serum MDA and SOD levels, as well as the FF levels of OS markers. The expression of Nrf2, HO-1, and NQ-1 was significantly increased in the granulosa cells (GCs) of the AST group. Moreover, the MII oocyte and high-quality embryo rate were significantly increased in the AST group compared to the placebo group. We found no significant intergroup difference in the chemical and clinical pregnancy rates. Conclusion: AST treatment has been shown to increase both serum TAC levels and activation of the Nrf2 axis in PCOS patients� GCs. Trial Registration: ClincialTrials.gov Identifier: NCT03991286. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature
The phenotypic spectrum of PCDH12 associated disorders - Five new cases and review of the literature
No full textPCDH12 is a member of the non-clustered protocadherin family of calcium-dependent cell adhesion proteins, which are involved in the regulation of brain development and endothelial adhesion. To date, only 15 families have been reported with PCDH12 associated disease. The main features previously associated with PCDH12 deficiency are developmental delay, movement disorder, epilepsy, microcephaly, visual impairment, midbrain malformations, and intracranial calcifications. Here, we report novel clinical features such as onset of epilepsy after infancy, episodes of transient developmental regression, and dysplasia of the medulla oblongata associated with three different novel truncating PCDH12 mutations in five cases (three children, two adults) from three unrelated families. Interestingly, our data suggests a clinical overlap with interferonopathies, and we show an elevated interferon score in two pediatric patients. This case series expands the genetic and phenotypic spectrum of PCDH12 associated diseases and highlights the broad clinical variability. © 2021 European Paediatric Neurology Societ
Evaluation of serum alanine aminotransferase and aspartate aminotransferase enzyme levels in women patients with chronic periodontitis
No full textThe authors� aim in this study was to investigate the relationship between chronic periodontitis and liver status using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in women patients. The researchers conducted a case-control study on women patients referred to Dental School. The researchers collected 5 ml of peripheral venous blood from women for the laboratory process after performing periodontal examination. Participants were 124 women aged 25�50 years (62 cases and 62 control). The difference in serum levels of ALT and the difference in serum levels of AST between the two groups were not statistically significant. However, there was a significant correlation between liver enzymes and periodontitis parameters. © 2021 Taylor & Francis Group, LLC
Prevalence of reflux nephropathy in Iranian children with solitary kidney: results of a multi-center study
No full textBackground: Given the importance of the function of the remnant kidney in children with unilateral renal agenesis and the significance of timely diagnosis and treatment of reflux nephropathy to prevent further damage to the remaining kidney, we aimed to determine the prevalence of reflux nephropathy in this subgroup of pediatric patients. Methods: In general, 274 children referred to pediatric nephrologists in different parts of Iran were evaluated, of whom 199 had solitary kidney and were included in this cross-sectional study. The reasons for referral included urinary tract infection (UTI), abnormal renal ultrasonography, being symptomatic, and incidental screening. Demographic characteristics, including age and gender were recorded. History of UTI and presence of vesicoureteral reflux (VUR) were evaluated. Results: Of the 274 children evaluated in this study with the mean age (SD) of 4.71 (4.24) years, 199 (72.6) had solitary kidney. Among these, 118 (59.3) were male and 81 (60.7) were female, 21.1 had a history of UTI, and VUR was present in 23.1. The most common cause of referral was abnormal renal ultrasonography (40.2), followed by incidental screening (21.1), being symptomatic (14.1), and UTI (5.5). In 116 children (58.3), the right kidneys and in 83 (41.7) the left kidneys were absent. Besides, 14.6 of the participants had consanguineous parents and 3 had a family history of solitary kidney. Upon DMSA scan, the single kidney was scarred in 13.1, of which only 7.5 were associated with VUR. In addition, proteinuria and hematuria were observed in 6.5 and 1.5 of children, respectively. Conclusions: The prevalence of reflux nephropathy was 7.5 in children with solitary kidney with a male predominance. Given the relatively high prevalence of reflux nephropathy in these children, screening for VUR in the remnant kidney appears to be essential in this population. © 2022, The Author(s)
Interactive relationship between Trp metabolites and gut microbiota: The impact on human pathology of disease
No full textTryptophan (Trp), an α-amino acid, is the precursor of serotonin (5-hydroxytryptamine, 5-HT), which is involved in a variety of features of metabolic function and human nutrition. Evidence highlights the role of Trp metabolites (exclusively 5-HT) in the gastrointestinal (GI) tract; however, the mechanisms of action involved in the release of 5-HT in the GI tract are still unknown. Considering the fact that variations of 5-HT may facilitate the growth of certain GI disorders, gaining a better understanding of the function and release of 5-HT in the GI tract would be beneficial. Additionally, investigating Trp metabolism may clarify the relationship between Trp and gut microbiota. It is believed that other metabolites of Trp (mostly that of the kynurenine pathway) may play a significant role in controlling gut microbiota function. In this review, we have attempted to summarize the current research investigating the relationship of gut microbiota, Trp and 5-HT metabolism (with particular attention paid to their metabolite type, as well as a discussion of the research methods used in each study). Taking together, regarding the role that Trp/5-HT plays in a range of physical and mental diseases, the gut bacterial types, as well as the related disorders, have been exclusively considered. © 2022 Society for Applied Microbiology
Anti-inflammatory effect of functionalized sulfasalazine boron nitride nanocages on cardiovascular disease and breast cancer: An in-silico simulation
No full textThe objective of this research work is to investigate the ability of sulfasalazine (as an anti-cytokine drug) functionalized B16N16, B15GeN16 and B15SiN16 nanocages to treat inflammatory cardiovascular disease and breast cancer in comparison with the pure sulfasalazine (SSZ). Density functional theory (DFT) calculations at PBE1 functional were used to investigate the structural, electronic and spectral properties of sulfasalazine decorated B16N16, B15GeN16 and B15SiN16 nanocages. The most stable state was obtained on adsorption of SSZ over B16N16, B15GeN16 and B15SiN16 nanocages via its pyridine ring. Also, the adsorption of SSZ through SO2 group over B16N16, B16GeN16 and B16SiN16 nanocages causes the lower binding energy and the increment of dipole moment as both factors can lead to increased sensitivity of the B16GeN16 nanocage to the drug. Molecular docking simulation illustrates that the interaction of SSZ via its pyridine ring with B15GeN16 gives the best binding affinity and inhibition potential of HER2 (human epidermal growth factor receptor 2) and TNF-α (tumor necrosis factor-alpha) whereas interaction of -SO2 group with B16N16 gives the best binding affinity and inhibition potential of COX-2 (cyclooxygenase-2) and IL-1 (Interleukin-1) receptors. The predicted results demonstrated that SSZ/B16N16 and SSZ/B16GeN16 complexes can serve as a promising and preventive agent for inflammatory cardiovascular disease and breast cancer. © 2022 Elsevier B.V
Recurrent viral RNA positivity and candidiasis findings in hospitalized patients with COVID-19
No full textBackground: The aim of this study was to evaluate reinfection and fungal infections among 785 patients with COVID-19 disease admitted to Baqiyatallah Hospital in Northeastern Iran after the onset of the COVID-19 epidemic. Materials & Methods: In this descriptive-analytic study (20 February-21 July 2020), reinfection and fungal infections among 785 patients were investigated using epidemiological questionnaire, clinical trials, Real-time PCR and CT scan (chest computed tomography) from the hospital HIS (hospital's information system) and collected samples. Results: Reinfection and one oral candidiasis were diagnosed in one 68-year-old man and one 47-year-old man 63 and 42 days after the initial infection, respectively. Conclusion: The research results showed that exposure to COVID-19 may not establish long-term protective immunity to all patients. © 2022 Future Medicine Ltd